M14-387: This phase I/II trial is combining two chemotherapy drugs (venetoclax and cytarabine) in people who haven't received treatment for Acute Myelogenous Leukemia (AML)A Phase 1/2 Study of ABT-199 in Combination With Low-Dose Cytarabine in Treatment-Naive Subjects With Acute Myelogenous Leukemia Who Are at Least 65 Years of Age and Who Are Not Eligible for Standard Anthracycline-Based Induction Therapy

Inclusion

• Participant must be greater than or equal to 65 years of age in Phase 1 and 2. Participants enrolled in Cohort C must be either:

  • greater than or equal to 75 years of age; OR

  • greater than or equal to 60 to 74 years will be eligible if the participants has at least one of the following co-morbidities, which make the participant unfit for intensive chemotherapy:

    • Eastern Cooperative Oncology Group (ECOG) Performance Status of 2 - 3;
    • Cardiac history of congestive heart failure (CHF) requiring treatment or ejection fraction less than or equal to 50% or chronic stable angina;
    • Diffusion capacity of carbon monoxide (DLCO) less than or equal to 65% or forced expiratory volume in one second (FEV1) less than or equal to 65%;
    • Creatinine clearance greater than or equal to 30 mL/min to less than 45 ml/min (calculated by Cockcroft-Gault formula)
    • Moderate hepatic impairment with total bilirubin greater than 1.5 to less than or equal to 3.0 × upper limit of normal (ULN)
    • Any other comorbidity that the physician judges to be incompatible with intensive chemotherapy must be reviewed and approved by the study medical monitor before study enrollment
• Participant must have a projected life expectancy of at least 12 weeks.
• Participant must have histological confirmation of AML and be ineligible for treatment with a standard cytarabine and anthracycline induction regimen due to co-morbidity or other factors.
• Participant must have received no prior treatment for AML with the exception of hydroxyurea, allowed through the first cycle of study treatment. Note: Participant may have been treated for prior Myelodysplastic Syndrome.

• Participant must have an ECOG performance status:

  • of 0 to 2 for participants greater than equal to 75 years of age
  • of 0 to 3 for participants greater than equal to 60 to 74 years of age, if 0 - 1 another co-morbidity is required to make participant eligible.
• Participant must have adequate renal function as demonstrated by a creatinine clearance greater than or equal to 30 mL/min; determined via urine collection for 24-hour creatinine clearance or by the Cockcroft Gault formula.

• Participant must have adequate liver function as demonstrated by:

  • aspartate aminotransferase (AST) less than or equal to 2.5 × ULN
  • alanine aminotransferase (ALT) less than or equal to 2.5 × ULN

  • bilirubin less than or equal to 1.5 × ULN for all participants age 75 and older

    • Participants who are less than 75 years of age must have a bilirubin of less than 3.0 × ULN.

Note: Participants with Gilbert's Syndrome may have a bilirubin greater than 1.5 × ULN per discussion between the investigator and AbbVie medical monitor.

• Male participants must agree to refrain from unprotected sex and sperm donation from initial study drug administration until 180 days after the last dose of study drug.
• Participant must voluntarily sign and date an informed consent, approved by an Independent Ethics Committee (IEC)/Institutional Review Board (IRB), prior to the initiation of any screening or study-specific procedures.

• If female, participant must be either:

  • Postmenopausal defined as no menses for 12 or more months without an alternative medical cause OR
  • Permanently surgical sterile (bilateral oophorectomy, bilateral salpingectomy or hysterectomy)